I would start by picking a voltage. It would be easy to pick either 5V or 3.3V and all components would be one or the other, no level translation required or allowed.
Having done that, I would design the motherboard with all the IO gadgets I would ever want. Knobs, switches, dials, lights, whatever. Toss in an I2C LCD display, whatever. Maybe a little prototyping board in the middle...
Then I would design CPU daughter cards for each the various CPUs (ARM, PIC, PIC32, whatever). I might also have Arduino headers on the motherboard so I could use Arduino Shields.
I'm not sure how I would orient the daughter cards. Mounting them parallel to the motherboard would block up a lot of real estate. Maybe I would use edge connectors and mount the daughter boards vertically on one edge of the motherboard. Out of the way of all the peripherals. In any event, the daughter board would take care of signal routing.
One limitation that is annoying: I will pick a number of connections between the daughter card and the motherboard. Having done this, I am limited in the number of pins I can have on the CPU. Is 40 enough? 64, 100, ?
The motherboard would be pretty large. I would need to find a source for cheap PCBs of that size.
For my needs, I would never do this. I tend to buy uCs in the 'stamp' format. I can then plug them into breadboards or even into sockets on the final project board. I have several projects where the 'stamp' CPU board is soldered in place.
CPUs like this:
https://www.pololu.com/product/2150